356 DIABETES CARE, VOLUME 24, NUMBER 2, FEBRUARY 2001 but this appeared to result predominantly from the relationship with type 2 diabetes/GIT in this population of Chinese subjects. Diabetes Care 24:356–361, 2001 I n the metabolic syndrome, which is reaching epidemic proportions in popu- lations in modernized Asian nations (1), hypertension is clustered together with dia- betes and dyslipidemia (1,2). The develop- ment of hypertension in the presence or absence of diabetes may result from a differ- ent pattern of interplay between genetic and environmental factors, implying that the pathogenic mechanisms for hypertension may differ. Indeed, preliminary studies of the blood pressure response to antihypertensive agents indicate that differences exist between hypertensive subjects with or without dia- betes, with angiotensin II type 1 receptor (AT 1 R) antagonists being less effective in dia- betic patients relative to calcium-channel antagonists (3). It is therefore important to assess the contribution of genetic factors in well-defined homogeneous populations and to consider hypertension in diabetic and nondiabetic groups separately. The renin-angiotensin system (RAS) is fundamental to blood pressure regulation; as such, each component is potentially involved in the etiology of the polygenic disorder known as primary hypertension. Treatment with both ACE inhibitors (4) and AT 1 R antagonists (5) may reduce the risks from cardiovascular diseases, further impli- cating the involvement of the RAS in the development of vascular disease. Further- more, studies have reported a genetic con- tribution to RAS activity (6). Three RAS gene polymorphisms—the angiotensino- gen (AGT) M235T (7–12), the ACE inser- tion/deletion (I/D) (9,12–18), and the AT 1 R A1166C (9,19,20) polymorphisms—have been extensively described in the literature. Meta-analyses have suggested weak associa- From the Divisions of Clinical Pharmacology (G.N.T., B.T., J.C.N.C., J.A.J.H.C.), Cardiology (J.E.S.), and Endocrinology (J.C.N.C., C.S.C.), Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong, China. Address correspondence and reprint requests to G. Neil Thomas, PhD, Division of Clinical Pharmacol- ogy, Department of Medicine and Therapeutics, The Prince of Wales Hospital, Shatin, NT, Hong Kong SAR, China. E-mail: thomas1997@cuhk.edu.hk. Received for publication 5 June 2000 and accepted in revised form 19 October 2000. Abbreviations: AGT, angiotensinogen; ANOVA, analysis of variance; AT 1 R, angiotensin II type 1 recep- tor; CHD, coronary heart disease; dBP, diastolic blood pressure; FIGP, fasting insulin-glucose product; FIGPa, adjusted FIGP; FPG, fasting plasma glucose; GIT, glucose intolerance; HOMA, homeostasis model assessment; I/D, insertion/deletion; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; RAS, renin-angiotensin system; sBP, systolic blood pressure; WHR, waist-to-hip ratio. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Renin-Angiotensin System Gene Polymorphisms, Blood Pressure, Dyslipidemia, and Diabetes in Hong Kong Chinese A significant association of the ACE insertion/deletion polymorphism with type 2 diabetes ORIGINAL ARTICLE OBJECTIVE — In Chinese populations, hypertension is common and is a major risk factor for cerebrovascular and coronary heart disease, particularly when associated with diabetes. The clus- tering of these disorders and dyslipidemia and obesity is termed the metabolic syndrome and is increasing in prevalence in the populations of modernizing Asian nations. The renin-angiotensin system (RAS) helps maintain blood pressure and salt homeostasis and may play a role in the pathogenesis of aspects of the metabolic syndrome. We investigated three RAS gene polymor- phisms—the ACE insertion/deletion (I/D), angiotensinogen (AGT) M235T, and angiotensin II type 1 receptor (AT 1 R) A1166C polymorphisms—for a possible role in modulating these disor- ders in 853 Chinese subjects with varying components of the metabolic syndrome. RESEARCH DESIGN AND METHODS — The three gene polymorphisms of this cross- sectional study were detected using polymerase chain reaction–based protocols. The genotype frequencies were compared between the controls (n = 119) and both overlapping and nonover- lapping groups of patients with type 2 diabetes, hypertension, and dyslipidemia using  2 test. Dif- ferences in levels of the biochemical parameters between the genotypes were determined using analysis of variance. RESULTS — No significant relationship was identified between these polymorphisms and blood pressure in this population. Although the AT 1 R A1166C polymorphism was not associated with any aspect of the metabolic syndrome examined, there was limited evidence to suggest that the AGT M235T polymorphism may be associated with cholesterol levels. The ACE I allele was significantly more frequent in each group comprising subjects with type 2 diabetes/glucose intol- erance (GIT), and the I allele was associated with higher fasting plasma glucose levels. CONCLUSIONS — These findings suggest that these polymorphisms are unlikely to be involved in the pathogenesis of hypertension. The ACE I/D polymorphism was associated with the metabolic syndrome, having a higher frequency of I allele–containing genotypes in those groups, G. NEIL THOMAS, PHD BRIAN TOMLINSON, FRCP JULIANA C.N. CHAN, FRCP JOHN E. SANDERSON, FRCP CLIVE S. COCKRAM, FRCP JULIAN A.J.H. CRITCHLEY , FRCP Pathophysiology/Complications